The overall objective of this project is to define DENV transmission vi/ithin a family in the presence of an ill, dengue viremic family member. This prospective family cohort study m\\ identify immunologic correlates of protection, disease and the full spectrum ofthe host response from primary to secondary DENV infection. This study will also define infection among adults and herd immunity that influences the force of infection. DENV is an important arboviral infection causing a severe febrile illness and its more serious manifestation, dengue hemorrhagic fever (DHF). Our previous prospective cohort studies on dengue pathogenesis and epidemiology has contributed to the understanding of dengue virus transmission and the virus-host interactions leading to mild or severe dengue infection. What is unknown about dengue transmission and pathogenesis include correlates of immunity that define protection or illness, herd immunity defining the force of infection, and illness in adults and the consequences of fading immunity. Our previous studies point to the household of a DENV viremic patient as a potential source of DENV transmission and ultimately dengue transmission may be defined by the family unit members and their degree of risk or protection from infection. In this proposal's novel study design, we will prospectively follow family cohorts and be able to detect the ill viremic family member who becomes the sentinel case for additional transmission within the family and neighborhood. This study will be able to define familial herd immunity and force of infection within a family and risk to the neighborhood, characterize and define the correlates of protective immunity (T-cell, neutralizing antibody titer) among family members who are protected from infection or develop subclinical disease, and define the spectrum ofthe virus-host response through sequential infections and virus serotypes. This proposal will be the first study of its kind with its findings having implications on our understanding of the virus-host pathogenesis that defines the gradient of disease severity from subclinical to severe DENV infection and the development of effective DENV vaccines.